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Current Drug Delivery

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ISSN (Print): 1567-2018
ISSN (Online): 1875-5704

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Research Article

Sterically Stabilized Polyionic Complex Nanogels of Chitosan Lysate and PEG-b-Polyglutamic Acid Copolymer for the Delivery of Irinotecan Active Metabolite (SN-38)

Author(s): Mohsen Salmanpour, Mahvand Saeed-Vaghefi, Samira Sadat Abolmaali and Ali Mohamad Tamaddon*

Volume 18, Issue 6, 2021

Published on: 03 November, 2020

Page: [741 - 752] Pages: 12

DOI: 10.2174/1567201817999201103195846

Price: $65

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Abstract

Background: Poly Ionic Complex (PIC) nanogels are promising delivery systems with numerous attractions such as simple, fast, and organic solvent-free particle formation and mild drug loading conditions. Among polyelectrolytes, poly (L-amino acid) copolymers, such as poly (ethylene glycol)-block-poly (L-glutamic acid) copolymers (PEG-b-PGlu) are interesting biocompatible and biodegradable candidates bearing carboxylic acid functional groups.

Objective: Aiming to solubilize and to preserve short-acting irinotecan active metabolite (SN38), sterically stabilized PIC nanogels were prepared through electrostatic charge neutralization between PEG-b-PGlu and chitosan lysate, a polycationic natural polymer obtained through digestion of chitosan by hydrogen peroxide oxidation and is soluble in a wide range of pH.

Methods: Synthesis of PEG-b-PGlu was accomplished by N-carboxy anhydride polymerization of γ -benzyl L-glutamic acid, which is initiated by methoxy PEG-NH2 and successive debenzylation reaction.

Results: The resulting block copolymer was characterized by FTIR, 1H-NMR, and Size Exclusion Chromatography (SEC). Self-assembling properties of the PIC nanogels were investigated by pyrene assay, Dynamic Light Scattering (DLS), and Transmission Electron Microscopy (TEM), indicating the formation of homogeneous spherical particles with a mean size of 28 nm at the PEGb- PGlu concentrations/LMWC weight ratio of 5:1. Upon direct loading of SN38, the drug solubility enhanced more than 4×103 folds with a mean loading efficiency of 89% and the drug loading of 30%. PIC nanogels exhibited zeta potential of +1 mV, acceptable biocompatibility, and superior cytotoxicity in murine colorectal carcinoma (CT26 cell line) compared to free drug.

Conclusion: In addition, the PIC nanogels provided SN38 protection against hydrolytic degradation in physiologic conditions. Conclusively, the well-tuned PIC nanogels are suggested as a potentially biocompatible nanocarrier for SN38 delivery.

Keywords: SN38, polyionic complex, nanogel, poly (L-amino acid), chitosan lysate, LMWC.

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[1]
Mathijssen, R.H.; Verweij, J.; Loos, W.J.; de Bruijn, P.; Nooter, K.; Sparreboom, A. Irinotecan pharmacokinetics-pharmacodynamics: The clinical relevance of prolonged exposure to SN-38. Br. J. Cancer, 2002, 87(2), 144-150.
[http://dx.doi.org/10.1038/sj.bjc.6600447] [PMID: 12107833]
[2]
Sapra, P.; Zhao, H.; Mehlig, M.; Malaby, J.; Kraft, P.; Longley, C.; Greenberger, L.M.; Horak, I.D. Novel delivery of SN38 markedly inhibits tumor growth in xenografts, including a camptothecin-11-refractory model. Clin. Cancer Res., 2008, 14(6), 1888-1896.
[http://dx.doi.org/10.1158/1078-0432.CCR-07-4456] [PMID: 18347192]
[3]
Xie, R.; Mathijssen, R.H.; Sparreboom, A.; Verweij, J.; Karlsson, M.O. Clinical pharmacokinetics of irinotecan and its metabolites: A population analysis. J. Clin. Oncol., 2002, 20(15), 3293-3301.
[http://dx.doi.org/10.1200/JCO.2002.11.073] [PMID: 12149304]
[4]
Burke, T.G.; Mi, Z. Ethyl substitution at the 7 position extends the half-life of 10-hydroxycamptothecin in the presence of human serum albumin. J. Med. Chem., 1993, 36(17), 2580-2582.
[http://dx.doi.org/10.1021/jm00069a020] [PMID: 8355258]
[5]
Mi, Z.; Burke, T.G. Marked interspecies variations concerning the interactions of camptothecin with serum albumins: A frequency- domain fluorescence spectroscopic study. Biochemistry, 1994, 33(42), 12540-12545.
[http://dx.doi.org/10.1021/bi00208a002] [PMID: 7918477]
[6]
Mao, S.; Bakowsky, U.; Jintapattanakit, A.; Kissel, T. Self-assembled polyelectrolyte nanocomplexes between chitosan derivatives and insulin. J. Pharm. Sci., 2006, 95(5), 1035-1048.
[http://dx.doi.org/10.1002/jps.20520] [PMID: 16565978]
[7]
Cegnar, M.; Kerč, J. Self-assembled polyelectrolyte nanocomplexes of alginate, chitosan and ovalbumin. Acta Chim. Slov., 2010, 57(2), 431-441.
[PMID: 24061741]
[8]
Ogunleye, A.; Bhat, A.; Irorere, V.U.; Hill, D.; Williams, C.; Radecka, I. Poly-γ-glutamic acid: Production, properties and applications. Microbiology (Reading), 2015, 161(1), 1-17.
[http://dx.doi.org/10.1099/mic.0.081448-0] [PMID: 25288645]
[9]
Bajaj, I.; Singhal, R. Poly (glutamic acid)-An emerging biopolymer of commercial interest. Bioresour. Technol., 2011, 102(10), 5551-5561.
[http://dx.doi.org/10.1016/j.biortech.2011.02.047] [PMID: 21377358]
[10]
Akagi, T.; Watanabe, K.; Kim, H.; Akashi, M. Stabilization of polyion complex nanoparticles composed of poly(amino acid) using hydrophobic interactions. Langmuir, 2010, 26(4), 2406-2413.
[http://dx.doi.org/10.1021/la902868g] [PMID: 20017513]
[11]
Mostoufi, H.; Yousefi, G.; Tamaddon, A.M.; Firuzi, O. Reversing multi-drug tumor resistance to Paclitaxel by well-defined pH-sensitive amphiphilic polypeptide block copolymers via induction of lysosomal membrane permeabilization. Colloids Surf. B Biointerfaces, 2019, 174, 17-27.
[http://dx.doi.org/10.1016/j.colsurfb.2018.10.072] [PMID: 30408674]
[12]
Abolmaali, S.S.; Tamaddon, A.M.; Salmanpour, M.; Mohammadi, S.; Dinarvand, R. Block ionomer micellar nanoparticles from double hydrophilic copolymers, classifications and promises for delivery of cancer chemotherapeutics. Eur. J. Pharm. Sci., 2017, 104, 393-405.
[http://dx.doi.org/10.1016/j.ejps.2017.04.009] [PMID: 28416470]
[13]
Liang, J.; Huang, C.; Gong, X. Silicon nanocrystals and their composites: Syntheses, fluorescence mechanisms, and biological applications. ACS Sustain. Chem.& Eng., 2019, 7(22), 18213-18227.
[http://dx.doi.org/10.1021/acssuschemeng.9b04359]
[14]
Peng, J.; Zhao, X.; Wang, W.; Gong, X. Durable self-cleaning surfaces with superhydrophobic and highly oleophobic properties. Langmuir, 2019, 35(25), 8404-8412.
[http://dx.doi.org/10.1021/acs.langmuir.9b01507] [PMID: 31192609]
[15]
Zhong, L.; Gong, X. Phase separation-induced superhydrophobic polylactic acid films. Soft Matter, 2019, 15(46), 9500-9506.
[http://dx.doi.org/10.1039/C9SM01624D] [PMID: 31702749]
[16]
Li, Z.; Zhao, X.; Huang, C.; Gong, X. Recent advances in green fabrication of luminescent solar concentrators using nontoxic quantum dots as fluorophores. J. Mater. Chem. C Mater. Opt. Electron. Devices, 2019, 7(40), 12373-12387.
[http://dx.doi.org/10.1039/C9TC03520F]
[17]
Gong, X.; Zhang, J.; Jiang, S. Ionic liquid-induced nanoporous structures of polymer films. Chem. Commun. (Camb.), 2020, 56(20), 3054-3057.
[http://dx.doi.org/10.1039/C9CC08768K] [PMID: 32048643]
[18]
Lavasanifar, A.; Samuel, J.; Kwon, G.S. Poly(ethylene oxide)-block-poly(L-amino acid) micelles for drug delivery. Adv. Drug Deliv. Rev., 2002, 54(2), 169-190.
[http://dx.doi.org/10.1016/S0169-409X(02)00015-7] [PMID: 11897144]
[19]
Bae, Y.; Kataoka, K. Intelligent polymeric micelles from functional poly(ethylene glycol)-poly(amino acid) block copolymers. Adv. Drug Deliv. Rev., 2009, 61(10), 768-784.
[http://dx.doi.org/10.1016/j.addr.2009.04.016] [PMID: 19422866]
[20]
Osada, K; Christie, RJ; Kataoka, K Polymeric micelles from poly (ethylene glycol)–poly (amino acid) block copolymer for drug and gene delivery. J. R. Soc. Interface, 2009, 6(3), S325-39.
[21]
Salmanpour, M.; Tamaddon, A.; Yousefi, G.; Mohammadi-Samani, S. “Grafting-from” synthesis and characterization of poly (2-ethyl-2-oxazoline)-b-poly (benzyl L-glutamate) micellar nanoparticles for potential biomedical applications. Bioimpacts, 2017, 7(3), 155-166.
[http://dx.doi.org/10.15171/bi.2017.19] [PMID: 29159143]
[22]
Mero, A.; Pasut, G.; Dalla Via, L.; Fijten, M.W.; Schubert, U.S.; Hoogenboom, R.; Veronese, F.M. Synthesis and characterization of poly(2-ethyl 2-oxazoline)-conjugates with proteins and drugs: Suitable alternatives to PEG-conjugates? J. Control. Release, 2008, 125(2), 87-95.
[http://dx.doi.org/10.1016/j.jconrel.2007.10.010] [PMID: 18031860]
[23]
Kronek, J.; Paulovicova, E.; Paulovicova, L.; Kroneková, Z.; Luston, J. Biocompatibility and immunocompatibility assessment of poly (2-oxazolines). Practical applications in Biomedical engineering Rijeka: InTech., 2012, 257-84.
[24]
Golkar, N.; Tamaddon, A.M.; Samani, S.M. Effect of lipid composition on incorporation of trastuzumab-PEG-lipid into nanoliposomes by post-insertion method: Physicochemical and cellular characterization. J. Liposome Res., 2016, 26(2), 113-125.
[PMID: 26023889]
[25]
Bhumkar, D.R.; Pokharkar, V.B. Studies on effect of pH on cross-linking of chitosan with sodium tripolyphosphate: A technical note. AAPS Pharm. SciTech, 2006, 7(2), E50.
[http://dx.doi.org/10.1208/pt070250] [PMID: 16796367]
[26]
Mohammadi-Samani, S.; Miri, R.; Salmanpour, M.; Khalighian, N.; Sotoudeh, S.; Erfani, N. Preparation and assessment of chitosan-coated superparamagnetic Fe3O4 nanoparticles for controlled delivery of methotrexate. Res. Pharm. Sci., 2013, 8(1), 25-33.
[PMID: 24459473]
[27]
Amoozgar, Z.; Park, J.; Lin, Q.; Yeo, Y. Low molecular-weight chitosan as a pH-sensitive stealth coating for tumor-specific drug delivery. Mol. Pharm., 2012, 9(5), 1262-1270.
[http://dx.doi.org/10.1021/mp2005615] [PMID: 22489704]
[28]
Lee, M.; Nah, J-W.; Kwon, Y.; Koh, J.J.; Ko, K.S.; Kim, S.W. Water-soluble and low molecular weight chitosan-based plasmid DNA delivery. Pharm. Res., 2001, 18(4), 427-431.
[http://dx.doi.org/10.1023/A:1011037807261] [PMID: 11451027]
[29]
Chae, S.Y.; Jang, M.K.; Nah, J.W. Influence of molecular weight on oral absorption of water soluble chitosans. J. Control. Release, 2005, 102(2), 383-394.
[http://dx.doi.org/10.1016/j.jconrel.2004.10.012] [PMID: 15653159]
[30]
Hashemi, F.; Tamaddon, A.; Yousefi, G.; Farvadi, F. Effect of pH on Solubilisation of Practically Insoluble Sorafenib by Classic and Stealth Polyamidoamine (PAMAM) Dendrimers and-cyclodextrin; Sumy State University, 2012.
[31]
Wang, L-l.; Wu, Y-x.; Xu, R-w.; Wu, G-y.; Yang, W-t. Synthesis and characterization of poly (L-glutamic acid-co-L-aspartic acid). Chin. J. Polym. Sci., 2008, 26(04), 381-391.
[http://dx.doi.org/10.1142/S0256767908003047]
[32]
Sherma, J.; Fried, B. Thin-layer and paper chromatography. Anal. Chem., 1984, 56(5), 48R-63R.
[http://dx.doi.org/10.1021/ac00269a004] [PMID: 3046431]
[33]
Golkar, N.; Samani, S.M.; Tamaddon, A.M. Modulated cellular delivery of anti-VEGF siRNA (bevasiranib) by incorporating supramolecular assemblies of hydrophobically modified polyamidoamine dendrimer in stealth liposomes. Int. J. Pharm., 2016, 510(1), 30-41.
[http://dx.doi.org/10.1016/j.ijpharm.2016.06.026] [PMID: 27291973]
[34]
Serrano, L.A.; Yang, Y.; Salvati, E.; Stellacci, F.; Krol, S.; Guldin, S. pH-Mediated molecular differentiation for fluorimetric quantification of chemotherapeutic drugs in human plasma. Chem. Commun. (Camb.), 2018, 54(12), 1485-1488.
[http://dx.doi.org/10.1039/C7CC07668A] [PMID: 29359205]
[35]
Shin, W.S.; Han, J.; Kumar, R.; Lee, G.G.; Sessler, J.L.; Kim, J-H.; Kim, J.S. Programmed activation of cancer cell apoptosis: A tumor-targeted phototherapeutic topoisomerase I inhibitor. Sci. Rep., 2016, 6(1), 29018.
[http://dx.doi.org/10.1038/srep29018] [PMID: 27374023]
[36]
Abolmaali, S.; Tamaddon, A.; Dinarvand, R. Nano-hydrogels of methoxy polyethylene glycol-grafted branched polyethyleneimine via biodegradable cross-linking of Zn2+-ionomer micelle template. J. Nanopart. Res., 2013, 15(12), 1-21.
[http://dx.doi.org/10.1007/s11051-013-2134-z]
[37]
Tian, F.; Liu, Y.; Hu, K.; Zhao, B. Study of the depolymerization behavior of chitosan by hydrogen peroxide. Carbohydr. Polym., 2004, 57(1), 31-37.
[http://dx.doi.org/10.1016/j.carbpol.2004.03.016]
[38]
Jia, Z.; Shen, D. Effect of reaction temperature and reaction time on the preparation of low-molecular-weight chitosan using phosphoric acid. Carbohydr. Polym., 2002, 49(4), 393-396.
[http://dx.doi.org/10.1016/S0144-8617(02)00026-7]
[39]
Kubota, N.; Tatsumoto, N.; Sano, T.; Toya, K. A simple preparation of half N-acetylated chitosan highly soluble in water and aqueous organic solvents. Carbohydr. Res., 2000, 324(4), 268-274.
[http://dx.doi.org/10.1016/S0008-6215(99)00263-3] [PMID: 10744335]
[40]
Cheng, J.; Deming, T.J. Synthesis of polypeptides by ring-opening polymerization of α-amino acid N-carboxyanhydrides. Top. Curr. Chem., 2012, 310, 1-26.
[PMID: 21647839]
[41]
Yang, W-x.; Wang, L-l.; Zhu, H.; Xu, R-w.; Wu, Y-x. Synthesis of poly(glutamic acid-co-aspartic acid) via combination of N-carboxyanhydride ring opening polymerization with debenzylation. Chin. J. Polym. Sci., 2013, 31(12), 1706-1716.
[http://dx.doi.org/10.1007/s10118-013-1363-z]
[42]
Izunobi, J.U.; Higginbotham, C.L. Polymer molecular weight analysis by1H NMR spectroscopy. J. Chem. Educ., 2011, 88(8), 1098-1104.
[http://dx.doi.org/10.1021/ed100461v]
[43]
Lim, C.; Youn, Y.S.; Lee, K.S.; Hoang, N.H.; Sim, T.; Lee, E.S.; Oh, K.T. Development of a robust pH-sensitive polyelectrolyte ionomer complex for anticancer nanocarriers. Int. J. Nanomedicine, 2016, 11, 703-713.
[PMID: 26955270]
[44]
Peng, Z.; Sun, Y.; Liu, X.; Tong, Z. Nanoparticles of block ionomer complexes from double hydrophilic Poly(acrylic acid)-b-poly(ethylene oxide)-b-poly(acrylic acid) triblock copolymer and oppositely charged surfactant. Nanoscale Res. Lett., 2009, 5(1), 89-95.
[http://dx.doi.org/10.1007/s11671-009-9448-x] [PMID: 20651926]
[45]
Honary, S. Zahir FJTJoPR. Effect of zeta potential on the properties of nano-drug delivery systems-A review. Trop. J. Pharm. Res., 2013, 12(2), 265-273.
[46]
Salmanpour, M.; Yousefi, G.; Samani, S.M.; Mohammadi, S.; Anbardar, M.H.; Tamaddon, A. Nanoparticulate delivery of irinotecan active metabolite (SN38) in murine colorectal carcinoma through conjugation to poly (2-ethyl 2-oxazoline)-b-poly (L-glutamic acid) double hydrophilic copolymer. Eur. J. Pharm. Sci., 2019, 136, 104941.
[http://dx.doi.org/10.1016/j.ejps.2019.05.019] [PMID: 31136788]
[47]
Ebrahimnejad, P.; Dinarvand, R.; Sajadi, A.; Jaafari, M.R.; Nomani, A.R.; Azizi, E.; Rad-Malekshahi, M.; Atyabi, F. Preparation and in vitro evaluation of actively targetable nanoparticles for SN-38 delivery against HT-29 cell lines. Nanomedicine (Lond.), 2010, 6(3), 478-485.
[http://dx.doi.org/10.1016/j.nano.2009.10.003] [PMID: 19836467]
[48]
Ebrahimnejad, P.; Dinarvand, R.; Jafari, M.R.; Tabasi, S.A.; Atyabi, F. Characterization, blood profile and biodistribution properties of surface modified PLGA nanoparticles of SN-38. Int. J. Pharm., 2011, 406(1-2), 122-127.
[http://dx.doi.org/10.1016/j.ijpharm.2010.12.022] [PMID: 21185365]
[49]
Gu, Q.; Xing, J.Z.; Huang, M.; He, C.; Chen, J. SN-38 loaded polymeric micelles to enhance cancer therapy. Nanotechnology, 2012, 23(20), 205101.
[http://dx.doi.org/10.1088/0957-4484/23/20/205101] [PMID: 22543761]
[50]
Koizumi, F.; Kitagawa, M.; Negishi, T.; Onda, T.; Matsumoto, S.; Hamaguchi, T.; Matsumura, Y. Novel SN-38-incorporating polymeric micelles, NK012, eradicate vascular endothelial growth factor-secreting bulky tumors. Cancer Res., 2006, 66(20), 10048-10056.
[http://dx.doi.org/10.1158/0008-5472.CAN-06-1605] [PMID: 17047068]
[51]
Thakur, R. Preformulation studies and development of MCM-41-7-ethyl-10-hydroxycamptothecin-loaded particles for drug delivery; Long Island University, The Brooklyn Center: Ann Arbor, 2011.
[52]
Sivakumar, B. Physico-chemical characterization of 7-Ethyl-10-Hydroxy Camptothecin (SN38) and formulation approaches towards improving its solubility and solution stability; Long Island University, The Brooklyn Center: Ann Arbor, 2010.
[53]
Xuan, T.; Zhang, J.A.; Ahmad, I. HPLC method for determination of SN-38 content and SN-38 entrapment efficiency in a novel liposome-based formulation, LE-SN38. J. Pharm. Biomed. Anal., 2006, 41(2), 582-588.
[http://dx.doi.org/10.1016/j.jpba.2005.10.051] [PMID: 16386867]
[54]
Moon, S.J.; Govindan, S.V.; Cardillo, T.M.; D’Souza, C.A.; Hansen, H.J.; Goldenberg, D.M. Antibody conjugates of 7-ethyl-10-hydroxycamptothecin (SN-38) for targeted cancer chemotherapy. J. Med. Chem., 2008, 51(21), 6916-6926.
[http://dx.doi.org/10.1021/jm800719t] [PMID: 18939816]
[55]
Liu, Y.; Piao, H.; Gao, Y.; Xu, C.; Tian, Y.; Wang, L.; Liu, J.; Tang, B.; Zou, M.; Cheng, G. Comparison of two self-assembled macromolecular prodrug micelles with different conjugate positions of SN38 for enhancing antitumor activity. Int. J. Nanomedicine, 2015, 10, 2295-2311.
[PMID: 25848251]
[56]
Zhang, J.A.; Xuan, T.; Parmar, M.; Ma, L.; Ugwu, S.; Ali, S.; Ahmad, I. Development and characterization of a novel liposome-based formulation of SN-38. Int. J. Pharm., 2004, 270(1-2), 93-107.
[http://dx.doi.org/10.1016/j.ijpharm.2003.10.015] [PMID: 14726126]

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